Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course

The “isomorphic subtype of diffuse astrocytoma” was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification

Genomic characterization of Nontuberculous Mycobacteria

YesMycobacterium tuberculosis and Mycobacterium leprae have remained, for many years, the primary species of the genus Mycobacterium of clinical and microbiological interest. The other members of the genus, referred to as nontuberculous mycobacteria (NTM), have long been underinvestigated. In the last decades, however, the number of reports linking various NTM species with human diseases has steadily increased and treatment difficulties have emerged. Despite the availability of whole genome sequencing technologies, limited effort has been devoted to the genetic characterization of NTM species. As a consequence, the taxonomic and phylogenetic structure of the genus remains unsettled and genomic information is lacking to support the identification of these organisms in a clinical setting. In this work, we widen the knowledge of NTMs by reconstructing and analyzing the genomes of 41 previously uncharacterized NTM species. We provide the first comprehensive characterization of the genomic diversity of NTMs and open new venues for the clinical identification of opportunistic pathogens from this genus

A New Version of DAISY to Test Structural Identifiability of Biological Models

Often ODE models in systems biology, medical research, epidemiology, ecology and many other areas, contain unknown parameters which need to be estimated from experimental data. Identifiability deals with the uniqueness of the relation between model parameters and ODE solution thus being a prerequisite for the well-posedness of parameter estimation. In this paper a novel extension of the software tool DAISY (Differential Algebra for Identifiability of SYstems) is presented. DAISY performs structural identifiability analysis for linear and nonlinear dynamic models described by polynomial or rational ODE\u2019s. The major upgrades of this new version regard the ability to include in the identifiability analysis either known and unknown model initial conditions, the possibility of entering a parameter estimate to calculate all the equivalent parameter solutions, the portability to MacOS platforms and an user-friendly interface. These upgrades make DAISY surely more general and easy to use. Practical examples are presented. DAISY is available at the web site daisy.dei.unipd.it

A Cyber-Physical Platform for Model Calibration

25 pages, 8 figuresSynthetic biology has so far made limited use of mathematical models, mostly because their inference has been traditionally perceived as expensive and/or difficult. We have recently demonstrated how in silico simulations and in vitro/vivo experiments can be integrated to develop a cyber-physical platform that automates model calibration and leads to saving 60–80% of the effort. In this book chapter, we illustrate the protocol used to attain such results. By providing a comprehensive list of steps and pointing the reader to the code we use to operate our platform, we aim at providing synthetic biologists with an additional tool to accelerate the pace at which the field progresses toward applicationsN